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Join Stephen Lieberman, a urologist, as we navigate the nuances of prostate care, discussing the evolution of PSA screening, the controversies it has sparked, and the crucial insights that can empower individuals to make informed decisions about their health.

Stephen Lieberman is a urologist.

He discusses the KevinMD article, “Is a PSA test right for me? A urologist answers.”

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast and get CME for this episode by clicking on the CME link in the show notes. Today we welcome Stephen Lieberman. He’s a urologist, and today’s KevinMD article is titled “Is a PSA test right for me? A urologist answers.” Stephen, welcome to the show.

Stephen Lieberman: Thank you, Kevin. Thanks for having me on.

Kevin Pho: So first, let’s briefly share your story and journey to where you are today.

Stephen Lieberman: Well, I went to college in Chicago, at Northwestern, and then went to medical school at USC-LA County. I graduated in 1977 and then went to Oregon. In those days we were doing internships, and I did a surgical rotating internship at OHSU. After being accepted into four different residencies, I decided on urology. I was actually hired by a man named Clarence Hodges, who wrote an article with Charles Huggins in 1941 describing the relationship between prostate cancer and testosterone, the male hormone. Dr. Huggins won the Nobel Prize for that work, so Hodges was a big deal, and he was the outgoing chairman of the department of urology at the time. Then I went to work for Kaiser in Portland, where I worked for 31 years as a general urologist with an interest in cancer, stones and pediatrics.

During that time, I developed a particular interest in PSA used for prostate cancer screening. While I was a resident, there was no such thing as PSA. We used acid phosphatase, and half of our patients, when I was a resident, had metastatic or advanced disease. In fact, at the VA in Portland, we had a ward full of people receiving IV Stilphostrol. When PSA came around in the mid-’80s, I had been working at Kaiser for probably three or four years. We started using PSA, and we noted a dramatic decrease in the number of patients presenting with metastatic disease, because they were being screened and treated. The number of radical prostatectomies I did during my residency was two or three, and by the time PSA was around, that really ramped up. I was doing two radical prostatectomies a week. And we noted a decrease not only in the number of patients presenting with metastatic disease but in the number of patients with metastatic disease overall. So incidence and prevalence went way down, from about 50 percent to about 10 percent.

Along with that came an increase in the number of patients treated for prostate cancer who didn’t necessarily need treatment, because we couldn’t tell the difference between indolent and clinically significant disease. From that arose the controversy, after the U.S. Preventive Services Task Force came out with its grade D recommendation, recommending against using PSA as a screening test. I was a very aggressive proponent of screening using PSA, because I thought that even though we couldn’t tell the difference between indolent and metastatic or advanced disease, we did know that the Gleason score was fairly predictive of who was going to have aggressive disease, and of who was a good candidate for treatment, namely surgery or radiation. So the Gleason score was very helpful at that time.

I’d go to grand rounds and give these lectures, and talk about the Gleason scoring system and about how we could minimize the complications of biopsies, surgery and radiation. I never really succeeded in convincing my primary care and internal medicine colleagues that they should be aggressive about screening, to the point where I went to see my own internist and said, “Are you going to do a PSA?” She said, “I don’t believe in that test.” I said, “Well, you realize who you’re talking to? Please do a PSA.” “Sure, sure.”

Then, around the mid-’90s, one of the residents came into my office and said, “I just had another patient present with a PSA of 600.” I said, “Wow, that’s pretty high.” He said, “Yeah, he’s got bone pain. He’s probably going to have metastatic prostate cancer.” I said, “Who are these people? Has he been screened? Has he been tested?” The resident said no. I said, “Well, how long has he been a member of Kaiser?” He said, “It looks like a long time, more than 10 years.” I said, “You know what? Let’s go back and see if we can pull out these patients who present with advanced or metastatic disease.”

So he went back. His name is Jaffer Bash, and he’s currently in practice in Salem. He found 100 consecutive patients who presented with metastatic prostate cancer. I said, “OK, great.” Their PSAs were all in the hundreds. I said, “Why don’t you go back and find out how many of them had health insurance 10 years prior to presenting?” So we went back to about 1985, and he found that 85 of the 100 could actually prove they had health insurance. I said, “OK, why don’t you review their charts and find out how many of them had had a PSA 10 years prior to presenting?” I thought maybe 10 percent. He came back with this: None of them had had a PSA. None of them had had a rectal exam. I said, “How many of them had had a shared decision-making conversation about the risks and benefits of having a PSA test?” None of them.

Since that time, there’s been an evolution: increasing specificity of PSA, and increasing sensitivity and specificity of transrectal biopsy. Yet there still remains this controversy, this argument between primary care and urologists.

Kevin Pho: Your KevinMD article is titled “Is a PSA test right for me? A urologist answers.” Just to give context, what are the current recommendations from the various major medical societies when it comes to prostate cancer screening?

Stephen Lieberman: That’s a great question, because the U.S. Preventive Services Task Force modified its grade D recommendation to a grade C recommendation. The grade D recommendation came out in 2012, and they upgraded it to grade C in 2018, based on the fact that, because they were not recommending screening, there was an increased number of patients presenting with metastatic disease. And morbidity and mortality from metastatic disease, as you know, are significant and costly. So most primary care people now go by that grade C recommendation, which recommends against using PSA as a screening test and says there’s no need to do a rectal exam either. The urologists have just revised their guideline for early detection of prostate cancer; I was a peer reviewer of that document. Both camps are recommending a shared decision-making conversation about the risks and benefits of prostate cancer screening. Well, I don’t think we should call it screening. I think we should call it early detection. If a person wants to know whether or not they are at risk of having clinically significant prostate cancer, then the first thing to do is a PSA test.

And since both camps are recommending a shared decision-making conversation, I can honestly tell you that it doesn’t happen, because of time constraints and because of a lack of the proper information. It doesn’t happen on the part of most primary care physicians. I have a lot of friends who are internists and primary care physicians, and I do consulting for an organization called MAVEN, which is the Medical Advice Volunteer Expert Network, where I do urology consults for primary care physicians at over 300 free clinics in the United States. I can tell you they don’t have the proper information or the proper knowledge to have a shared decision-making conversation about the risks and benefits of obtaining a PSA test.

Kevin Pho: Now, tell me: In an ideal world, if you do have that shared decision-making conversation with the patient, what are the risks and benefits of the PSA test that should be discussed during that conversation?

Stephen Lieberman: I don’t think there are any risks to having an $8 blood test. If a person has the test, I would recommend a risk assessment, and there are plenty of risk assessment calculators available online. I would first tell my primary care colleagues that there’s no such thing as an abnormal or normal PSA. PSAs are like a fingerprint. Everybody has their individual PSA, and that person has an individual risk of having clinically significant or clinically insignificant prostate cancer, and you can easily obtain that information by going online to a risk calculator.

The risk calculator asks you to plug in race, age and PSA. If they’ve done a percent free PSA, which helps improve the specificity and sensitivity of the test, you can put that in. If the percent free PSA is less than 10 percent, there’s a markedly increased risk of having clinically significant prostate cancer. If the percent free PSA is over 22 percent, there’s a markedly decreased risk of having clinically significant prostate cancer. So the first thing I would tell people is that there’s no such thing as a normal or abnormal PSA. You have an individual PSA, from which we can calculate your risk of having clinically insignificant and clinically significant prostate cancer.

Say you take a 53-year-old man who has a PSA of 4, and say it’s his first PSA; he’s never had a PSA before. If he’s white, if he has a normal rectal exam and if there’s no family history, his risk of having prostate cancer overall is going to be about 25 percent, but his risk of having clinically significant prostate cancer is 10 percent. So you tell that man, “Well, I can refer you to a urologist.” Ten years ago, the urologist would have had the same kind of conversation with him about whether or not he should have a biopsy. Nowadays, we have a whole slew of things to do before you even do a biopsy that make the PSA test and the risk assessment even more accurate, more sensitive and more specific, so that we’re actually reducing the number of biopsies that need to be done, dramatically. The main test I’m talking about is an MRI.

In Europe, in places like Sweden, primary care people are now doing PSAs on people who want to know whether or not they’re at risk of having clinically significant prostate cancer. Say their PSA is greater than 1.5. If they’re in their 40s or 50s, 1.5 would be regarded by most clinicians as normal. It’s not. If a 40-year-old has a PSA of 1.5, that person has a 60 percent risk of having clinically significant prostate cancer sometime during their life. Those are the people you really want to follow and monitor.

So in Sweden, primary care people do the PSA test, and if it’s greater than 1.5, they then do what’s called a Stockholm3, and this is all before the patient even sees a urologist. The Stockholm3 is a test that’s a combination of, I think, five protein biomarkers and some genetic markers, and then they use clinical data and put it all into an algorithm, which gives them a Stockholm3 score. If the Stockholm3 score is significant, then they do an MRI. There’s a grading scale for MRIs, and a PI-RADS score of one or two is not indicative of clinically significant cancer, so those people are followed; they’re usually not biopsied. If it’s three, they’re referred to a urologist for biopsy, and nowadays a lot of people are going to transperineal biopsies, which reduce the risk of infection after biopsy. A PI-RADS score of four or five means there’s a lesion there, and they do systematic biopsies on it. That has dramatically improved the detection of clinically significant prostate cancer and has eliminated the risk of being diagnosed with clinically insignificant prostate cancer. Unfortunately, in this country, we have not kept up with that kind of evolution, and that’s why this discrepancy, these two camps, exist.

Kevin Pho: Sure. From the perspective of the U.S. Preventive Services Task Force, what were some of the arguments that initially gave prostate cancer screening a D recommendation, and now a C? What were some of the arguments in their favor?

Stephen Lieberman: Well, they had legitimate arguments. The arguments were that we were diagnosing too many indolent, clinically insignificant cancers and operating on these people or radiating them, and that was causing significant morbidity, because back then a lot of patients were impotent after surgery, and a lot of patients were incontinent after surgery. I can tell you that a lot of my patients weren’t impotent or incontinent, because we were diagnosing them early. If you diagnose a person early, you can do nerve-sparing prostatectomies, and that spares their potency. I would say that fewer than 20 percent of my patients were incontinent, and of those, only a handful, less than 2 percent, were dramatically incontinent, requiring an operation to fix the incontinence.

Be that as it may, with the development of robotic prostatectomies, there have been significant improvements in the incidence of impotence and incontinence. But the U.S. Preventive Services Task Force was right in saying that urologists were taking way too many prostates out that didn’t need to be taken out, causing too much morbidity from surgery or radiation, and therefore they weren’t recommending screening. Now, their definition of screening was screening everybody, no matter their age, no matter their risk factors. And they recommended not even doing a PSA test or rectal exam on anybody over 70, and I think that recommendation still holds today, which is, in my opinion, wrong. But that’s why they had their grade D recommendation, and it was modified to grade C in 2018.

Kevin Pho: Given the advancements in screening technology, like MRI, which you mentioned, and some of these other diagnostic advancements, do you anticipate the U.S. Preventive Services Task Force revisiting the recommendation in the foreseeable future?

Stephen Lieberman: I would hope so. I would hope so. If you look at the AUA guideline on early detection, which was published, I believe, in April of this year, that guideline is very different from what the U.S. Preventive Services Task Force is currently recommending. Unfortunately, most primary care organizations, the family medicine people and the AMA, are still locked into this grade C task force recommendation.

I can tell you that if you look at the document the U.S. Preventive Services Task Force published, there are many, many flaws. The task force uses three studies as the basis for the recommendation: the PLCO study, which is in the United States, then the European study and then the Göteborg study. Those studies are largely flawed, and misinterpreted by the task force. I was actually in the room at the AUA meeting in 2012 when they presented this recommendation. There was a panel with each author of each study, and a statistician from the University of Washington, and about a thousand urologists in the room. They presented the study, and at the end of the presentation they asked for a show of hands: “Does anybody in this room support the study?” Not one hand was raised. Then the statistician got up and basically said, “You’ve misinterpreted these studies.” And every author of the studies got up and said, “We don’t agree with this interpretation of the study. We don’t agree with your recommendation. It’s wrong.” There’s lots of material in the literature about how the U.S. Preventive Services Task Force misinterpreted the data from these studies.

Kevin Pho: Well, let me ask from a patient standpoint. There are obviously conflicting guidelines. For someone listening to you on this podcast, what are some of the questions patients should ask their primary care physicians when it comes to the issue of prostate cancer screening?

Stephen Lieberman: Well, it depends on their age. If a 40-year-old comes to me and says, “Should I have a PSA?”, I would say, “Yeah, I think you should.” And they’ll say, “Well, what if it’s normal?” I would tell them there’s no such thing as normal. There’s risk associated with every PSA, and at 40 years old, your risk depends on whether or not your PSA is greater than 1.5. If it’s greater than 1.5, then you’re at risk: You have a 60 percent chance of having clinically significant prostate cancer over the rest of your life. If it’s greater than 1.5, I would probably get an MRI on you, which carries no risk at all. If the MRI is positive, that is, a PI-RADS of three, four or five, I would refer you to a urologist for consideration of a biopsy, or of other tests that would refine your risk. And those other tests are simple. They’re blood tests and urine tests, and that’s all they are: a simple blood test or a simple urine test, which will really enable me to tell you whether your risk is increased beyond what it may be from just a simple PSA, or decreased. It may be that your risk is decreased and you won’t need anything except to be followed. And if you’re followed, then the actual benefit of having the PSA test now, even if it’s negative, is that we’re going to know whether or not you’re going to have cancer sooner than if we didn’t do the test at all. So that’s the way I would have that conversation.

Kevin Pho: We’re talking to Stephen Lieberman. He’s a urologist, and his KevinMD article is titled “Is a PSA test right for me? A urologist answers.” Stephen, tell us some of the take-home messages that you want to leave with the KevinMD audience.

Stephen Lieberman: OK. There’s no such thing as a normal or abnormal PSA. Everybody has an individual risk of having clinically significant prostate cancer, and that risk can be really refined and further defined by lots of new diagnostic capabilities, including MRI and urine and blood tests, like Stockholm3 and the 4K test. Early detection of clinically significant prostate cancer is definitely positive and dramatically reduces the incidence and prevalence of advanced and metastatic disease. The current strategies we’re using do not increase the detection of clinically insignificant or indolent disease, nor do they increase the number of unnecessary biopsies that are done. In fact, we’re seeing a decreased number of biopsies. The risks of early detection strategies have been significantly reduced by the introduction of MRI, and the risks of biopsies have been reduced by using transperineal biopsies.

Risk assessment can be further enhanced by all these tests we’ve talked about: percent free PSA, PSA velocity, PSA density, IsoPSA, urine tests like PCA3, and ExoDx, which is a good new urine test, Stockholm3, 4Kscore, and genetic markers, which are used in people who have a family history. So there are lots of things in our armamentarium to reduce your risk of having something done to you unnecessarily, whether it be a biopsy, surgery or radiation, and they will greatly increase your ability to avoid metastatic or advanced disease. If you do have metastatic disease, you’re subject to increased risks from the treatment of that metastatic disease, because being on Lupron for the rest of your life is not a picnic, having radiation for bone metastasis is not any fun either, and having a pathologic bone fracture is not great. And dying from prostate cancer, if you’re screened or detected early, is practically eliminated. If you remove a locally confined prostate cancer, clinically significant or not, the cure rate is 95 percent.

So if you’re 40 and asking whether or not you should have a PSA, my answer is yes, you should. If you’re 75 and have other medical comorbidities, you don’t need to have a PSA, and it’s all based on whether or not you’ve had a PSA before, and all that. But thank you for having me on. I really appreciate the opportunity.

Kevin Pho: Sure. Stephen, thank you so much for sharing your time and insight, and thanks again for coming on the show.